The key attributes of T lymphocytes that allow them to function in adaptive immunity are established as progenitors undergo development in the thymus. The step of positive selection, in particular, ensures expression of an MHC restricted, clonally expressed receptor, which has appropriate effector potential and is equipped to traffic to and survive in lymphoid organs. Although much is known about the ligands and signals that drive positive selection, less is known about the genetic program that supports the process. This proposal will test the role of two genetic changes that occur during positive selection, and determine what functional outcomes they support. One of these involves the TGF[unreadable]/BMP family receptors, Endoglin and ALK1. These two proteins form an alternate receptor for TGF[unreadable], and we propose to test if this is critical to develop functional competence in naive T cells. The second one is a transcription factor KLF2, which we hypothesize is required for mature thymocytes to emigrate from the thymus and access peripheral lymph nodes to survive and participate in immune responses.